Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity
Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity
复制标题
DOI：
10.1038/sj.npp.1300905
复制
发表时间：
2006-06-01
影响因子：
7.6
通讯作者：
Markou, Athina
中科院分区：
文献类型：
--
作者：
Kenny, Paul J.;Markou, Athina
尼古丁是烟草烟雾中的主要成分，有助于人类吸烟者形成和保持有害的烟草习惯。尼古丁的强化作用可能是通过刺激大脑回路的能力而产生的，大脑回路介导了对自然奖励的检测和体验。然而，关于尼古丁在体内对大脑奖励系统的急性或长期作用，人们知之甚少。在这里，我们研究了静脉注射尼古丁(0.03 mg/kg/次，无碱)对脑奖赏系统敏感性的影响，反映在大鼠脑内自我刺激(ICSS)阈值的变化上。大鼠每天给尼古丁1h或12h给药，每次给药前1h和给药后15min评估奖赏阈值。对照组大鼠自始至终保持尼古丁的幼稚。尼古丁自身给药增加了大脑奖赏系统的敏感性，这是通过尼古丁后降低1和12小时大鼠的奖赏阈值来检测的。这种尼古丁增强的奖赏系统敏感性被高亲和力的尼古丁受体拮抗剂二氢β-红景天碱(DHβE；3 mg/kg)逆转。令人惊讶的是，尼古丁诱导的奖赏系统兴奋在尼古丁自我给药停止后至少持续了36天。总体而言，这些数据表明，大鼠可以自愿摄入足够数量的尼古丁，以提高大脑奖励系统的敏感度，这一行动可能对建立和维持尼古丁习惯至关重要。此外，自我管理的尼古丁将奖赏系统的敏感度重置到一个新的增加水平，从而在奖赏系统中留下不可磨灭的“记忆”，到目前为止，这一行为似乎是尼古丁在滥用药物中独有的。
Nicotine is a major component of tobacco smoke contributing to the initiation and persistence of the harmful tobacco habit in human smokers. The reinforcing effects of nicotine likely arise through its ability to stimulate brain circuitry mediating the detection and experiencing of natural rewards. Nevertheless, remarkably little is known concerning the acute or long-lasting actions of nicotine on brain reward systems in vivo. Here, we investigated the effects of intravenously self-administered nicotine (0.03 mg/kg/infusion, free base) on the sensitivity of brain reward systems, reflected in alterations of intracranial self-stimulation (ICSS) thresholds in rats. Rats self-administered nicotine during 1 or 12 h daily sessions, with reward thresholds assessed 1 h before and 15 min after each self-administration session. Control rats remained nicotine naive throughout. Nicotine self-administration increased the sensitivity of brain reward systems, detected by post-nicotine lowering of reward thresholds in 1 and 12 h rats. This nicotine-enhanced sensitivity of reward systems was reversed by the high-affinity nicotinic receptor antagonist dihydro-beta-erythroidine (DH beta E; 3 mg/kg). Surprisingly, nicotine-induced excitation of reward systems persisted for at least 36 days after nicotine self-administration had ceased. Overall, these data demonstrate that rats can voluntarily consume quantities of nicotine sufficient to increase the sensitivity of brain reward systems, an action likely crucial in establishing and maintaining the nicotine habit. Moreover, self-administered nicotine resets the sensitivity of reward systems to a new increased level, thereby imprinting an indelible 'memory' of its effects in reward systems, an action that so far appears unique to nicotine among drugs of abuse.